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Metabolic modulation: Pneumocystis phosphoglucomutase is a target influencing host recognition

Theodore J Kottom1, Eva M Carmona1, Bernd Lepenies2,3

  • 1Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Cell Surface (Amsterdam, Netherlands)
|July 18, 2024
PubMed

Insights

Phosphoglucomutase (PGM) is vital for fungal mannoprotein formation in Pneumocystis. Inhibiting PGM may offer a broad therapeutic strategy against fungal infections.

Area of Science:

  • Biochemistry
  • Mycology
  • Molecular Biology

Background:

  • Mannoproteins on the fungal surface are crucial for host-pathogen interactions.
  • The phosphoglucomutase (PGM) enzyme's role in Pneumocystis mannoprotein synthesis is not well understood.

Purpose of the Study:

  • To investigate the function of phosphoglucomutase (PGM) in Pneumocystis spp.
  • To explore the role of PGM in fungal cell wall mannoprotein formation.
  • To assess the potential of PGM as a therapeutic target.

Main Methods:

  • Expressing the Pneumocystis murina Pmpgm2 gene in a Saccharomyces cerevisiae pgm2Δ mutant strain.
  • Assessing mannose receptor (MR) binding and macrophage interaction.
  • Utilizing Gas Chromatography-Mass Spectroscopy (GC-MS) to quantify mannose content.

Main Results:

  • Complementation of the S. cerevisiae pgm2Δ strain with Pmpgm2 restored MR and macrophage binding to wild-type levels.
  • GC-MS analysis revealed reduced mannose content in the pgm2Δ yeast strain.
  • The study highlights PGM's role in dolichol glucosyl phosphate biosynthesis for cell wall integrity.

Conclusions:

  • Fungal PGM is essential for proper mannoprotein formation and cell wall biosynthesis.
  • Conserved targetable cysteine residues in PGM across fungal pathogens suggest potential for broad-spectrum therapeutic strategies.
  • PGM inhibition presents a promising avenue for developing new antifungal treatments.
Keywords:
C-type lectin receptors (CLRs)MannoproteinPhosphoglucomutasePneumocystis

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